Dopamine pathways & antipsychotics

Flavio Guzmn, MD
Pharmacology Instructor Health Sciences Faculty University of Mendoza Argentina

Psychiatry Resident Mental Health Teaching Hospital Dr. Carlos Pereyra Mendoza Argentina

Learning objective
Understand basic concepts of dopaminergic pathways and their relevance to antipsychotic effects.

Dopaminergic pathways: outline

- Mesolimbic pathway (positive

symptoms) - Mesocortical pathway (negative symptoms) - Nigrostriatal pathway (EPS and TD) -Tuberoinfundibular pathway (hyperprolactinemia)

Mesolimbic pathway & positive symptoms of schizophrenia

Anatomy Projections from the ventral tegmental area (VTA) to the nucleus accumbens. Physiology Motivation, emotions, reward , positive symptoms of schizophrenia Implications D2 antagonists reduce positive symptoms of schizophrenia.

Mesocortical pathway: negative & cognitive symptoms

Anatomy Projections from the ventral tegmental area (VTA) to the cortex (PFC).

Physiology
Cognition and executive functions (DLPFC), emotions and affect (VMPFC).

Implications
Hypofunction of the mesocortical pathway might be related to cognitive and negative symptoms in schizophrenia

Nigrostriatal pathway & EPS

Anatomy Projections from substantia nigra (pars compacta) to striatum (caudate and putamen). Physiology Stimulation of purposeful movement. Implications D2 antagonism induces extrapyramidal symptoms (pseudoparkinsonism)

Tuberoinfundibular pathway & prolactin release

Anatomy Hypothalamus (arcuate and periventricular nuclei) to infundibular region (median eminence). Physiology Dopamine is released into the portal circulation connecting the median eminence with the anterior pituitary gland. Dopamine tonically inhibits prolactin release. Implications D2 antagonism increases prolactin levels.

Summary
Hyperactivation from the VTA to limbic areas might be related to positive symptoms of schizophrenia. Hypofunction of the mesocortical pathway might in part explain cognitive and negative symptoms of schizophrenia. D2 blockade of the nigrostriatal pathway can cause EPS. D2 blockade of the tuberoinfundibular pathway increases prolactin blood levels.